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CD33 in Alzheimer's Disease

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Abstract

The amyloid-beta peptide (Aβ) cascade hypothesis posits that Aβ accumulation is the fundamental initiator of Alzheimer's disease (AD), and mounting evidence suggests that impaired Aβ clearance rather than its overproduction is the major pathogenic event for AD. Recent genetic studies have identified cluster of differentiation 33 (CD33) as a strong genetic locus linked to AD. As a type I transmembrane protein, CD33 belongs to the sialic acid-binding immunoglobulin-like lectins, mediating the cell–cell interaction and inhibiting normal functions of immune cells. In the brain, CD33 is mainly expressed on microglial cells. The level of CD33 was found to be increased in the AD brain, which positively correlated with amyloid plaque burden and disease severity. More importantly, CD33 led to the impairment of microglia-mediated clearance of Aβ, which resulted in the formation of amyloid plaques in the brain. In this article, we review the recent epidemiological findings of CD33 that related with AD and discuss the levels and pathogenic roles of CD33 in this disease. Based on the contributing effects of CD33 in AD pathogenesis, targeting CD33 may provide new opportunities for AD therapeutic strategies.

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Acknowledgments

This work was supported in part by grants from the National Natural Science Foundation of China (81000544 and 81171209), the Shandong Provincial Natural Science Foundation, China (ZR2010HQ004 and ZR2011HZ001), and the Shandong Provincial Outstanding Medical Academic Professional Program.

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The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, China

    Teng Jiang, Jin-Tai Yu, Xi-Chen Zhu & Lan Tan

  2. Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China

    Jin-Tai Yu, Nan Hu & Lan Tan

  3. Department of Neurology, Qingdao Municipal Hospital, College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, China

    Jin-Tai Yu, Meng-Shan Tan & Lan Tan

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  1. Teng Jiang
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Jiang, T., Yu, JT., Hu, N. et al. CD33 in Alzheimer's Disease. Mol Neurobiol 49, 529–535 (2014). https://doi.org/10.1007/s12035-013-8536-1

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